There is increasing evidence of an association between health behaviors and cognitive aging. Smoking, alcohol, physical activity and nutrition have all been found to be associated with poor cognitive function and dementia. The extent to which health behaviors can explain cognitive aging trajectories is of substantial public health relevance, particularly as they may be 'the'key modifiable risk factors for dementia. The overarching aim of this proposal is to examine the combined impact of health behaviors over the adult lifecourse in determining cognitive aging trajectories starting from midlife. The specific aims are: 1. To examine the combined impact of smoking, alcohol consumption, physical activity and diet on cognitive decline in order to assess whether the impact of health behaviors in early, mid and late midlife is most important and whether this effect accumulates over time. 2. To examine the extent to which change in one behavior leads to changes in others and the extent to which these changes influence cognitive aging. 3. To examine bidirectional associations between health behaviors and cognitive aging starting in midlife: 4. To examine the extent to which biological changes, such as those in vascular risk factors and diseases, explain the association between health behaviors and cognitive aging. We will also examine the role played by two potential effect modifiers of the association between health behaviors and cognitive aging: socioeconomic status (SES) and the apolipoprotein E (APOE) e4 allele. In addition, our work will focus on issues to do measurement of health behaviors: Detailed attention will be paid to the categorization of the health behaviors in order to understand the shape of the association between each measure of behavior and cognitive aging, whether different measures diet have similar associations with cognitive aging and whether there are discrepancies between the objective and subjective measures of physical activity. We will also examine the impact of health behaviors on specific domains of cognitive aging, with memory and executive function as two major aspects. The Whitehall II test battery was introduced to the full Whitehall II cohort at phase 5 when participants were on average 55 years old and had already been assessed for behaviors over the previous 10 years. A third wave of cognitive data is currently being collected, and will be available late 2009, allowing us look at trajectories of cognitive change. Although the proposal is based primarily on the British Whitehall, the research team is composed of scientists based in France as well as the UK, providing us with the opportunity to validate some of our results in data from the French GAZEL study. PUBLIC HEALTH RELEVANCE: Continuing increases in life expectancy come in tandem with knowledge that the prevalence of dementia rises with age, doubling every 4-5 years after the age of 60. By age 80 over one third of the population is likely to be living with dementia;for industrialized countries an unprecedented challenge in terms of care provision. Although dementia generally occurs late in life, it is increasingly recognized that there is a long preclinical phase, making the evaluation of risk factors prior to and during this phase a crucial next step in the battle to prevent or delay the onset of dementia. Driven by this "long" view of dementia our research focuses on the determinants of heterogeneity in cognitive aging starting from early midlife. Existing research suggests an association between health behaviors and cognitive aging;smoking, alcohol, physical activity and nutrition have all been found to be associated with poor cognitive function and dementia. What remains unknown is the extent to which these behaviors, acting in combination, determine cognitive aging trajectories. In public health terms, why is this knowledge so important? Because these behaviors are likely to be 'the'key risk factors for dementia that are both modifiable and amenable to low-cost intervention at the national level. In research terms, the unique feature of this proposal is three repeat assessments of cognitive function using a comprehensive test battery with a first assessment carried out in early midlife allowing an examination of the inflection point in changes in cognitive functioning.